Adherence to mucosal surfaces is necessary for bacterial colonization. The in-vitro adherence to type 25 Streptococcus pneumoniae to buccal epithelial cells was studied in 15 smokers, 15 nonsmokers, and 21 exsmokers. Background adherence in smokers and nonsmokers was similar, but smokers had a markedly increased pneumococcal adherence compared to nonsmokers (12.3 +/- 6.9 vs 0.7 +/- 0.4). This increase was not related to subject age or duration of cigarette use. Pneumococcal adherence in some exsmokers remained elevated for up to three years after smoking cessation. Incubation of nonsmokers' cells with smoker's saliva resulted in increased pneumococcal adherence to the nonsmokers' cells (1.1 +/- 0.099 to 8.2 +/- 4.4), suggesting mediation of pneumococcal adherence by a noncellular constituent of smokers' saliva. The increased pneumococcal adherence in cigarette smokers may promote oropharyngeal colonization and contribute to the increased risk of respiratory infection in cigarette smokers.